Hepatocellular carcinoma (HCC) is a blatant example of a cancer health disparity in that HCC is disproportionally higher in incidence and mortality among Asian Americans compared with non-Hispanic Whites. Infection by the Hepatitis B virus (HBV) is the principal risk factor for HCC among Asian Americans. HCC survival rates have significantly improved among those whose cancer is detected early and treated aggressively, but remain short among those with advanced, and rapidly progressive disease. Thus elucidating biological mechanisms underlying the behavior of HBV-mediated HCC will potentially contribute to improved surveillance, treatment, control and prevention. Our long term goal is to understand epidemiologic causes, sociocultural barriers, and biologic mechanisms of HBV-related disparities, and to develop tools which can decrease the burden of these diseases on the Asian American community. In this study, we will compare viral factors and immune responses in HBV-infected Laotian and Hmong, who experience the highest HCC mortality rates among Asians, with HBV-infected Chinese and Vietnamese, who experience better survival rates. Importantly, Laotian and Hmong are also diagnosed at a younger age but with more advanced disease compared to other Asian ethnicities suggesting that there is a biologic basis to this disparity in HCC survival. Our central hypothesis is that differences in viral variants and host immune responses exist within the Laotian/Hmong population, which in part cause an earlier onset and more aggressive form of HCC, resulting in a disparity in HCC survival. We propose using next generation sequencing technologies to 1) compare viral factors associated with HCC prognosis in HBV-infected Laotian/Hmong to HBV-infected Chinese and Vietnamese and 2) assess immune responses associated with HCC survival in these same groups by gene expression activity of pro-inflammatory responses including NF?B-related genes and anti-inflammatory responses such as regulatory T cells, as well as T cell receptor usage and HLA allele frequencies. The impact of this study will be to improve the understanding of the biologic basis of disparities in HCC survival among Asian American ethnicities and may lead to better risk stratification and tailoring of treatment of HCC based upon host and viral factors.